The applicant has found that after uv-irradiation of wild type E. coli K-12, uracil or uridine at 10 minus to the 6th power M subsequently added to the medium kills up to 85% of the survivors. In contrast, if survivors of the radiation are given adenine or thymidine, there is a protective affect in that the number of survivors increase. The results indicate that certain antagonistic intracellular ribonucleotides or thymidylate may regulate repair of uv-damage. Objectives of the proposal are 1. To determine if uracil inhibits excision repair of dimer damage or post-replication recombination repair. The experiments with wild-type cells involve effects of uracil in photo-reactivated cells, on excision of thymine dimers, and on host-cell reactivation of irradiated phages; and with polAl and uvr recA mutants to determine if DNA polymerase I or the recA gene product is a target of uracil action. 2. To determine if adenine or thymidine can block the action of uracil and whether pre-irradiation growth with uracil or with adenine effects survival from subsequent irradiation. 3. To explore the possibility that the mechanism of manganous ion mutagenesis involves DNA polymerase I activity with pyrimidine ribonucleotides in vivo in non-irradiated and irradiated cells; it is anticipated that if DNA polymerase I is involved, manganous ion, which permits utilization of ribonucleoside triphosphates by the enzyme in vitro, will enhance survival of irradiated cells offered uracil, and that uracil will augment the mutagenic action of manganous ion. PolAl cells deficient in the enzyme should be unaffected by uracil or by manganous ion. 4. To determine whether uracil or adenine effects survival from monofunctional alkylating agents or mitomycin C.